Two conceptions of the sources of conservatism in scientific research

The issue of the conservatism of scientific research questions the nature and the role of the internal and external forces controlling the emergence of new research questions or problems, the exploration of risky directions of research, or the use of risky research methods. This issue has recently gained a new framing in connection with the growing importance of the peer-review process and of the social and economic pressures weighing on the funding of scientific research. Current literature then interrogates the external and internal features that promote what are described as conservative tendencies in scientific research. In this paper, I propose to contribute to this debate by clarifying what might be internal sources of conservatism in science; that is, that are inherent to the research process itself. I distinguish two possible understandings of the sources and manifestations of this internal conservatism. I first present a representational description of the nature and origin of conservatism in science, which brings to the fore the difficulties researchers find in setting aside their conceptual framework. I then offer for consideration a larger perspective on conservatism by arguing for the existence of a practical conservatism generated by all the dimensions of scientific activities. In this framework, conservatism in science can be explained by the tendency of all practices to close in on their own local objectives. I illustrate this view by reference to an historical episode: the discovery of the chemical nature of genes by Avery

Serendipity: an Argument for Scientific Freedom?

The unpredictability of the development and results of a research program is often invoked in favor of a free, desinterested science that would be led mainly by scientific curiosity, in contrast with a use-inspired science led by definite practical expectations. This paper will challenge a crucial but underexamined assumption in this line of defense of scientific freedom, namely that a free science is the best system of science to generate unexpected results. We will propose conditions favoring the occurrence of unexpected facts in the course of a scientific investigation and then establish that use-inspired science actually scores better in this area

L’imprévisibilité de la science : un argument pour la liberté de recherche ? La découverte des ARNi comme étude de cas

The unpredictability of the development of science is often invoked to defend the epistemic value of a free, curiosity-driven, disinterested research, against its finalization by practical objectives. My work aims at initiating a rigorous critical analysis of this “unpredictability argument”. To do so, I consider a case study: the discovery of the RNA interference. I show that the use of this episode to defend a principle of scientific autonomy is misleading. In this case indeed, the unpredictable part of the discovery emerged from use inspired science, whereas basic research only generated predictable results. I suggest that the unpredictability argument, often used in a superficial way, misses its target by mixing the question of the genesis and that of the management of the unexpected. The distinction of these two aspects of the problem is necessary, I contend, to evaluate the value and the limits of the unpredictability argument. Le caractère imprévisible du développement et des résultats de la science est souvent invoqué pour défendre la valeur épistémique d’une recherche libre, désintéressée, guidée par la seule curiosité, contre sa finalisation par des objectifs pratiques. Notre travail a pour vocation de poser les jalons d’une analyse critique rigoureuse de cet « argument d’imprévisibilité ». Pour ce faire, nous proposons de considérer une étude de cas : la découverte du phénomène d’interférence à ARN. Nous montrons que l’utilisation régulière de cet épisode pour défendre un principe d’autonomie scientifique est fautive. Dans ce cas en effet, la part d’inattendu a émergé d’une science « inspirée par l’usage », alors que de la recherche « fondamentale » n’a émergé que du prévisible, tant au niveau des démarches mises en œuvre que des résultats obtenus. Nous suggérons alors que l’argument d’imprévisibilité, mobilisé souvent de manière trop intuitive et superficielle, rate sa cible en négligeant de séparer la question de la genèse et celle de la gestion de l’inattendu. La distinction de ces deux aspects du problème nous semble nécessaire pour évaluer avec précision la portée et les limites de l’argument d’imprévisibilité

La science doit-elle être autonome pour être utile ? La lutte contre le cancer comme étude de cas

La question des modes de gouvernance de la recherche se pose de manière pressante à nos démocraties contemporaines. La problème se manifeste concrètement à travers le degré d'autonomie à accorder à la sphère scientifique. Une idée classique stipule que la valeur épistémique de la science, seule garante d'une dynamique d'innovation optimale, augmente avec son niveau d'auto-gouvernance. Un argument utilisé de manière récurrente invoque l'imprévisibilité inhérente au processus de découverte pour justifier la plus grande richesse épistémique d'une démarche intellectuelle mue par la seule curiosité. En particulier, le fait de donner un poids trop grand à la science appliquée, nécessairement finalisée par des objectifs pratiques, est souvent dénoncé comme un facteur d'appauvrissement du savoir général, et, par voie de conséquence, de tarissement de l'innovation. Ce mémoire a pour but d'analyser en détail les bases empiriques de ce jugement, en tentant de comprendre la part de chacun des types de recherche dans la construction de connaissances sur le monde d'une part, et dans la création d'outils –technologiques, thérapeutiques– nouveaux. Ce type de questions n'ayant que des réponses locales, nous choisissons le cas de la lutte contre le cancer, du début du XXe siècle à aujourd'hui. Cette analyse historique permet d'amener plusieurs types d'arguments contre l'idée d'une supériorité épistémique systématique de la science fondamentale autonome sur une science appliquée, plus finalisée. Nous montrons tout d'abord, à travers l'étude des modes de raisonnement propres à la pratique clinique, que la complexité du processus de découverte rend l'argument de l'imprévisibilité insuffisamment fouillé pour être réellement pertinent. En un second temps, l'analyse de la construction et des développements de la théorie génétique du cancer met en évidence la valeur épistémique certaine d'une science inspirée par l'usage. Enfin, l'analyse des controverses récentes entre les deux principales théories étiologique du cancer (la SMT et la TOFT) permet d'introduire la notion de pluralisme pragmatique: la science inspirée par l'usage est plus tolérante à la pluralité des théories explicatives. Cette idée affaiblit l'idée d'une plus grande diversité épistémique d'une science s'auto-gouvernant, guidée par la seule curiosité intellectuelle. L'étude de la recherche menée dans le cadre des Plans Cancer permet alors d'illustrer cette notion à travers le cas d'une recherche finalisée au niveau national

Contributions à l'étude de la réponse moléculaire à l'hypoxie : Modélisation mathématique et expérimentations sur cellules FUCCI

The biological effects of hypoxia are intensively studied today, mainly because of the crucial role played by oxygenation conditions during the development of cancers.For several years, a huge literature aims at describing the multiple aspects of the molecular, cellular and physiological responses to hypoxia. The complexity of the pathways which are involved and the diversity of their cellular effects make this task difficult.This situation is reflected in the plurality of the methods used, from the numerical simulations to the experimental approaches.In this thesis, I studied this subject using two tools: mathematical modeling and experimental approaches using HeLa-FUCCI cells.This recently developed cell line is an interesting tool not yetmuch exploited. By a genetic construction linking cell cycle proteins to a fluorophore, it makes possible the study of cell cycle dynamics using fluorescent microscopy.We could analyze various aspects of the cellular response to hypoxia, in a tumoral context. In a first time,we tried to mathematically characterize the links existing between cell cycle and the hypoxia pathways,driven by HiF-1.This model proposed a simple explanation to the cell cycle arrest notably observed in the tumor cells in hypoxicconditions.We then showed that the induction of chemoresistances could be considered as an entry into quiescence of tumor cells.In order to validate these observations we then tried to experimentally quantify the dynamics of cell proliferation using HeLa-FUCCI cells. As it appeared that the fluorophores were sensitive tothe lack of oxygen, we tested different molecules currently used to induceHiF-1 and mimic hypoxia (DFO and COCl2).From this study have emerged original results about the dynamics of cell cyclearrest of HeLa cells in presence of iron-chelators.If hypoxic conditions are not favorable to the use of HeLa-FUCCI cells, we could show that they were totally adapted to the study of cell cycle dynamics during reoxygenation.Interestingly, we then could observe a significant slowing down of the S-phase after the return to normoxia. In order to bring theoretical elements to this observation, we proposed a mathematical model of the dynamics of HiF-1 regulation in fluctuating oxygen conditions, based on thepVHL/HiF-1 couple, in the frame of a nucleo-cytoplasmic compartmentalization of HiF-1.This simple model well reproduce the main characteristics of the cell response to hypoxia.Besides, by simulating the consequences of a sudden reoxygenation, we observed the genesis of strong instabilities of HiF-1 intracellular level.Finally, we propose an experimental study of HiF-1 compartmentalization.Indeed, the FUCCI cells allow to simultaneously observe cell cycle progression (using fluorescent microscopy),and HiF-1 intra-cellular localization (with immunomarkage). We then could show that the variability of HiF-1 localization was not due to the progression into the cell cycle. Then, it is certainly linked to inter-cellular genetic differences, or to a stochasticity of HiF-1 regulation.Les effets biologiques de l'hypoxie sont très étudiés aujourd'hui, principalement en raison du rôle crucial que jouent les conditions d'oxygénation dans le développement des cancers.Depuis plusieurs années, une littérature foisonnante tente ainsi de décrire les multiples aspects de la réponse moléculaire, cellulaire et physiologique à l'hypoxie. La complexité des voies de signalisation impliquées et la diversité de leurs effets cellulaires rendent la tâche délicate. Cet état de fait se reflète dans la pluralité des méthodes utilisées, depuis les simulations numériques jusqu'aux approches expérimentales.Dans cette thèse, j'ai abordé ce sujet sur la base de deux outils: la modélisation mathématique et une démarche expérimentale utilisant les cellules HeLa-FUCCI. Cette lignée cellulaire récemment développée est en effet un instrument de choix encore peu exploité. Par une construction génétique liant des protéines du cycle cellulaire à un fluorophore, elle rend possible l'étude, en continue, de la dynamique du cycle en microscopie de fluorescence. Nous avons ainsi pu analyser plusieurs aspects de la réponse cellulaire à l'hypoxie, dans un contexte tumoral.Dans un premier temps, nous avons cherché à caractériser mathématiquement les liens tissés entre le cycle cellulaire et les voies de signalisation de l'hypoxie, centrées sur le facteur de transcription HiF-1. Ce modèle propose un explication simple à l'arrêt du cycle observé notamment dans les cellules tumorales en conditions hypoxiques. Nous avons ainsi montré que l'induction de chimiorésistance pouvait se concevoir comme une entrée facilitée en quiescence des cellules cancéreuses. Dans le but de valider ces observations, nous avons ensuite cherché à quantifier expérimentalement la dynamique de la prolifération cellulaire en utilisant les cellules HeLa-FUCCI. Comme il est apparu que les fluorophores qu'elles portent sont sensibles au manque d'oxygène, nous avons testé différentes molécules couramment utilisées pour induire HiF-1 et mimer l'hypoxie (DFO et CoCl2). De cette étude ont émergé des résultats originaux quant à la dynamique de blocage du cycle des cellules HeLa en présence de chélateurs du fer.Si les conditions hypoxiques ne sont pas favorables à l'utilisation des cellules FUCCI, nous avons pu en revanche montrer qu'elles étaient tout à fait adaptées à l'étude de la dynamique du cycle cellulaire en condition de réoxygénation. De manière intéressante, nous avons alors pu observer un ralentissement significatif de la phase S après retour à la normoxie. Afin d'apporter un éclairage théorique à cette observation, nous avons proposé un modèle mathématique de la dynamique de régulation de HiF-1 en conditions d'oxygène fluctuantes, basé sur le couple HiF-1/pVHL, dont les relations sont pensées dans un cadre compartimenté (noyau/cytoplasme). Ce modèle simple reproduit fidèlement les caractéristiques principales de la réponse cellulaire à l'hypoxie. En outre, en simulant les conséquences d'une réoxygénation brutale, nous avons observé la genèse de fortes instabilités du niveau intracellulaire de HiF-1. Enfin, nous avons mené une étude expérimentale de la compartimentation de HiF-1. L'outil FUCCI permet en effet d'observer simultanément l'avancement du cycle (en microscopie de fluorescence), et la localisation intra-cellulaire de HiF-1(par immunomarquage). Nous avons pu montrer que la variabilité de la localisation de HiF-1α n'était pas due à la progression dans le cycle. Elle est donc certainement liée soit à des différences génétiques inter-cellulaire, soit à une stochasticité de la régulation de HiF-1

Should we fund research randomly? An epistemological criticism of the lottery model as an alternative to peer-review for the funding of science

The way research is, and should be, funded by the public sphere is the subject of renewed interest for sociology, economics, management sciences, and more recently, for the philosophy of science. In this contribution, I propose a qualitative, epistemological criticism of the funding by lottery model, which is advocated by a growing number of scholars as an alternative to peer-review. This lottery scheme draws on the lack of efficiency and of robustness of the peer-review based evaluation to argue that the majority of public resources for basic science should be allocated randomly. I first differentiate between two distinct arguments used to defend this alternative funding scheme based on considerations about the logic of scientific research. To assess their epistemological limits, I then present and develop a conceptual frame, grounded on the notion of “system of practice”, which can be used to understand what precisely it means, for a research project, to be interesting or significant. I use this epistemological analysis to show that the lottery model is not theoretically optimal, since it underestimates the integration of all scientific projects in densely interconnected systems of conceptual, experimental, or technical practices which confer their proper interest to them. I also apply these arguments in order to criticize the classical peer-review process. I finally suggest, as a discussion, that some recently proposed models that bring to the fore a principle of decentralization of the evaluation and selection process may constitute a better alternative, if the practical conditions of their implementation are adequately settled

The Division of Cognitive Labor: Two Missing Dimensions of the Debate

The question of the division of cognitive labor (DCL) has given rise to various models characterizing the way scientists should distribute their efforts. These models often consider the scientific community as a self-governed sphere constituted by rational agents making choices on the basis of fixed rules. Such models have recently been criticized for not taking into account the real mechanisms of science funding. Hence, the question of the utility of the DCL models in guiding science policy remains an open one. In this paper, we show that two unconsidered dimensions would have to be taken into account. First, DCL studies miss the existence of distinct levels of epistemic objectives organizing the research process. Indeed, the scientific field is structured as a system of hierarchical, interconnected practices which are defined both by their inherent purposes and by various superposed external functions. Second, I criticize the absence of ontological considerations, since the epistemological significance of pluralism is highly dependent on the nature of the object under study. Because of these missing dimensions, current DCL models might have a limited usefulness to identify good practices of research governance

Measuring epistemic success of a biodiversity citizen science program: A citation study

This paper offers a comparative evaluation of the scientific impact of a citizen science program in ecology, ‘‘Vigie-Nature”, managed by the French National Museum of Natural History. Vigie-Nature consists of a national network of amateur observatories dedicated to a participative study of biodiversity in France that has been running for the last twenty years. We collected 123 articles published by Vigie-Nature in international peer-reviewed journals between 2007 and 2019, and computed the yearly amount of citations of these articles between 0–12 years post-publication. We then compared this body of citations with the number of yearly citations relative to the ensemble of the articles published in ecology and indexed in the ‘‘Web of Science” data-base. Using a longitudinal data analysis, we could observe that the yearly number of citations of the Vigie-Nature articles is significantly higher than that of the other publications in the same domain. Furthermore, this excess of citations tends to steadily grow over time: Vigie-Nature publications are about 1.5 times more cited 3 years after publication, and 3 times more cited 11 years post-publication. These results suggest that large-scale biodiversity citizen science projects are susceptible to reach a high epistemic impact, when managed in specific ways which need to be clarified through further investigations

Can Citizen Science Increase Trust in Research ? A Case Study of Delineating Polish Metropolitan Areas

We assess the relationship between citizens’ participation in scientific research and public trust in research results within social sciences. We conduct an online citizen science quasi-experiment concerning the delineation of metropolitan areas of Poland’s two major cities. It consists of two stages. In stage one, participants in one region are exposed to citizen science and directly involved in delineating the boundaries of their local metropolitan area. In stage two, we add another region in which participants are not involved in the research process. In both regions we ask the participants to evaluate the level of their trust in the presented maps of respective metropolitan areas: based on citizen science in one region and historical data regression analysis in the other region. Our contribution to the literature lies in two areas. First, we demonstrate how citizen science can be used in urban studies to delineate boundaries of urban and metropolitan areas exhibiting strong functional connections. Second, we show that the participation of local residents in the research process increases public trust in the study results compared to non-participatory ‘traditional academic’ research. These results confirm that citizen science programs deserve to be strongly supported by European institutions as a possible means to resolving the credibility crisis of science, research and evidence-based policies

Sciences participatives : enjeux épistémologiques

Participation of non-professional scientists to scientific and technical development is an old practice, currently gaining a strong renewed interest under the form of « citizen science » or « participative science ». These participation practices have considerably diversified in the last decades, in fields such as environmental sciences, biomedicine, astronomy or fundamental biology. This growth of « citizen science » programs has generated a pluridisciplinary literature aiming at describing these practices in their sociological, political, ethical and epistemological dimensions. This state-of-the-art presents the main epistemological issues posed by citizen participation, in all its forms, to the constitution of scientific knowledge in the natural sciences. It highlights both the opportunities and the challenges created by citizen science, as they are presented and studied in literature. One of the objective of this contribution is then to help constituting the issue of citizen participation as a fully-fledged research field for philosophy of scienc